m6A regulation of cortical and retinal neurogenesis is mediated by the redundant m6A readers YTHDFs
Open accessAbstract
m 6 A modification plays an important role in regulating mammalian neurogenesis. However, whether and how the major cytoplasmic m 6 A readers, YTHDF1, YTHDF2, and YTHDF3 mediate this process is still not clear. Here, we demonstrate that Ythdf1 and Ythdf2 double deletion but not individual knockout recapitulates the phenotype of Mettl14 knockout in cortex. In addition, we find that Mettl14 knockout in retina causes protracted proliferation of retinal progenitors, decreased numbers of retinal neurons, and disturbed laminar structure. This phenotype is only reproduced when Ythdf1 , Ythdf2 , and Ythdf3 are knocked out simultaneously in retina. Analysis of YTHDF target mRNAs in mouse cortex and retina reveals abundant overlapping mRNAs related to neurogenesis that are recognized and regulated by both YTHDF1 and YTHDF2. Together our results demonstrate that the functionally redundant YTHDFs mediate m 6 A regulation of cortical and retinal neurogenesis.
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YTHDF1/2/3 are redundant in their roles to promote degradation of m6A-modified RNAs.
“YTHDF1/2/3 are redundant in their roles to promote degradation of m6A-modified RNAs (Zaccara and Jaffrey 2020, 2024; Niu et al., 2022).”
From METTL3 uncouples chromatin accessibility from transcription during retinal development (2025) · cites this paper as Niu et al., 2022
The Discussion (page not available in our copy) says YTHDF1/2/3 regulate degradation and translation of target mRNAs, and reports that they function redundantly in retinal neurogenesis. It does not establish that the three readers are redundant specifically in promoting degradation of m6A-modified RNAs. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSimilar findings were reported for Mettl14 inactivation and triple deletion of m6A readers Ythdf1, Ythdf2, and Ythdf3.
“Similar findings were reported for Mettl14 inactivation and triple deletion of m6A readers Ythdf1, Ythdf2, and Ythdf3 (Niu et al., 2022; Li et al., 2023).”
From METTL3 uncouples chromatin accessibility from transcription during retinal development (2025) · cites this paper as Niu et al., 2022
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BindingDB Entry 50019381: Targeting m
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- Authors
- Niu, F., Che, P., Yang, Z., Zhang, J., Yang, L., Zhuang, M., Ou, X., & Ji, S.-J.
- Affiliations
- Harbin Institute of Technology (CN)
- Southern University of Science and Technology (CN)
- Corresponding author
- Ou, Xijun
- Ji, Sheng-Jian
- Venue
- iScience
- Publisher
- Elsevier BV
- Published
- 2022-09
- Volume
- 25
- Issue
- 9
- Pages
- 104908
- ISSN
- 2589-0042 (ISSN-L)
- PMC
- PMC9418916
- OpenAlex
- W4292170776
- Cited by
- 26
- References
- 35
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 1
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- iScience (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- m6A RNA methylation, YTHDF1, YTHDF2, YTHDF3, METTL14, m6A reader, cortical neurogenesis, retinal neurogenesis, retinal lamination, functional redundancy
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